title: Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.
abstract: NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.
authors.affiliation: Max-Planck Institute for Medical Research, Department of Molecular Neuroscience, Heidelberg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Sprengel
authors.forename: B
authors.initials: B
authors.lastname: Suchanek
authors.forename: C
authors.initials: C
authors.lastname: Amico
authors.forename: R
authors.initials: R
authors.lastname: Brusa
authors.forename: N
authors.initials: N
authors.lastname: Burnashev
authors.forename: A
authors.initials: A
authors.lastname: Rozov
authors.forename: O
authors.initials: O
authors.lastname: Hvalby
authors.forename: V
authors.initials: V
authors.lastname: Jensen
authors.forename: O
authors.initials: O
authors.lastname: Paulsen
authors.forename: P
authors.initials: P
authors.lastname: Andersen
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: R F
authors.initials: RF
authors.lastname: Thompson
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.forename: L C
authors.initials: LC
authors.lastname: Webster
authors.forename: S G
authors.initials: SG
authors.lastname: Grant
authors.forename: J
authors.initials: J
authors.lastname: Eilers
authors.forename: A
authors.initials: A
authors.lastname: Konnerth
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J O
authors.initials: JO
authors.lastname: McNamara
authors.forename: P H
authors.initials: PH
authors.lastname: Seeburg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons; D001921:Brain / Q000502:physiology*; D003213:Conditioning, Psychological; D019054:Evoked Potentials, Motor; D006624:Hippocampus / Q000502:physiology; D007696:Kindling, Neurologic / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009048:Motor Skills; D009419:Nerve Tissue Proteins / Q000032:analysis; D004856:Postural Balance; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D017384:Sequence Deletion; D009435:Synaptic Transmission
chemical_list: D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins